study to evaluate the safety of the study drug, GSK2857916, at different doses and how well it works to treat people with multiple myeloma when taken together with Lenalidomide Plus Dexamethasone (Treatment Arm A), or Bortezomib Plus Dexamethasone (Treatment Arm B).
- Conditions
- Relapsed / Refractory Multiple MyelomaMedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004689-93-ES
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 90
1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Male or female, 18 years or older (at the time consent is obtained).
3. Have confirmed diagnosis of Multiple Myeloma as defined by the International Myeloma Working Group (IMWG) (see Appendix 3, Section 13.3.1 of the Protocol).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
5. Have undergone stem cell transplant (STC), or are considered transplant ineligible.
6. Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy according to the IMWG criteria.
7. Must have at least ONE aspect of measurable disease, defined as one the following:
a. Urine M-protein excretion =200 mg/24h, or
b. Serum M-protein concentration =0.5 g/dL (=5.0 g/L), or
c. Serum free light chain (FLC) assay: involved FLC level =10 mg/dL
(=100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).
8. Participants with a history of autologous stem cell transplant (SCT) are eligible for study participation provided the following eligibility criteria are met:
a. Autologous SCT was >100 days prior to study enrollment
b. No active bacterial, viral, or fungal infection(s) present
c. Participant meets the remainder of the eligibility criteria outlined in this protocol
9. All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be = Grade 1 at the time of enrollment, except for alopecia and Grade 2 neuropathy.
10. Adequate organ system functions as defined by laboratory assessments (please refer to table 8 in the protocol).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 58
1. Systemic anti-myeloma therapy (including systemic steroids) within = 14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
2. Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
4. Prior allogenic stem cell transplant.
5. Evidence of active mucosal or internal bleeding.
6. Any major surgery within the last four weeks.
7. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria given in Table 8 in the Protocol
8. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
9. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator’s assessment).
10. Participants with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the participant’s illness. The participant must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
11. Evidence of cardiovascular risk including any of the following:
a. QTc interval =470 msec. NOTE: the QTc is the QT interval corrected for heart rate according to Fridericia’s formula (QTcF).
b. Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
c. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
d. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 6, Section 13.6 in the Protocol).
e. Uncontrolled hypertension.
12. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to GSK2857916, or any of the components of the study treatment.
13. Pregnant or lactating female.
14. Active infection requiring treatment.
15. Known HIV infection.
16. Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at Screening or within 3 months prior to first dose of study treatment)
17. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
18. Current corneal disease except for mild punctuate keratopathy (Appendix 10, Section 13.10 in the Protocol). Note: Patients with mild punctate keratopathy are allowed.
Additional Exclusion Criteria for Participants Assigned to Treatment Arm A (GSK2857916 plus
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method